Vitamin B6 Catabolites Act as Interkingdom Signals Within the Marine Microbiome

Abstract

More than half of all net primary productivity in the oceans is exchanged and recycled among marine microbial communities, through a network of complex interactions that fuel the global carbon cycle and control oceanic biogeochemistry1,2. Cryptic chemical signals control these interactions, thereby governing interspecies metabolite exchanges and structuring the ocean microbiome3. Here, we show that vitamin B6 catabolites--molecules long assumed to be inert byproducts of metabolism--in fact serve as potent, bidirectional, and widely distributed chemical signals that structure metabolite exchanges between marine eukaryotic phytoplankton and bacteria. We demonstrate that a ubiquitous diatom and its bacterial symbiont exchange five intermediates and catabolites in the glycerophospholipid and vitamin B6 metabolic pathways, previously not implicated in interspecies interactions. Acting in combination, these signals induce broad transcriptional responses that prime each organism to anticipate metabolic input from its partner and enter a symbiotic-like state, despite having no measurable effect on growth. We further identify and biochemically validate the enzymes biosynthesizing two of these signals: diatom-derived 4-pyridoxolactone and bacterially-derived 4-pyridoxate--a catabolite long regarded as bacterial waste4. Genes encoding these enzymes are globally distributed and co-expressed across diverse sunlit ocean microbial communities, indicating that vitamin B6-mediated communication is widespread in the ocean. Together, these findings reveal an unexpected signaling role for vitamin B6 and demonstrate that canonical metabolic byproducts can function as information-rich signals structuring interkingdom interactions in the oceans.